HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Serum amyloid A stimulates cultured endothelial cells to migrate and proliferate: inhibition by the multikinase inhibitor BIBF1120.

Abstract
In the present study, we tested whether serum amyloid A (SAA) protein, an established biomarker of inflammation, also plays a role in stimulating neovascularization. To evaluate this possibility, human carotid artery endothelial (HCtAE) cells were cultured and cellular migration and the proinflammatory and/or thrombotic activity of SAA (0, 1 or 10 μg/mL) on vascular endothelial cells was verified by determining gene regulation relative to control (in the absence of SAA). Exposure of HCtAE cells to SAA increased expression of the transcription factor nuclear factor-κB (NFKB), tumour necrosis factor (TNF) and pro-coagulative tissue factor (F3), and stimulated phosphorylation of the P65 subunit of the NFKB complex. Enhanced production of TNF and NFKB was paralleled by increased vascular endothelial growth factor (VEGF) mRNA and protein expression, as demonstrated by quantitative polymerase chain reaction, western blotting and ELISA. Administration of 10 μg/mL SAA enhanced endothelial cell migration (1.6-fold vs control), stimulated regrowth of HCtAE cells after mechanical injury (~1.2-fold vs control) and increased endothelial tube formation relative to control after 6 h. The SAA-mediated enhancement of endothelial cell migration, proliferation and tube formation were markedly inhibited by pretreatment of HCtAE cells with the multi-angiokinase receptor inhibitor BIBF1120 (100 nmol/L), although SAA-stimulated gene responses for F3 and NFKB were unaffected by 100 nmol/L BIBF1120 pretreatment. Overall, BIBF1120 inhibited the pro-angiogenic activity of SAA on vascular endothelial cells in this experimental model of inflammation.
AuthorsXiaoping Cai, S Ben Freedman, Paul K Witting
JournalClinical and experimental pharmacology & physiology (Clin Exp Pharmacol Physiol) Vol. 40 Issue 9 Pg. 662-70 (Sep 2013) ISSN: 1440-1681 [Electronic] Australia
PMID23819722 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2013 Wiley Publishing Asia Pty Ltd.
Chemical References
  • Carrier Proteins
  • HSAJ2425 protein, human
  • Indoles
  • Intracellular Signaling Peptides and Proteins
  • NF-kappa B
  • Neoplasm Proteins
  • Serum Amyloid A Protein
  • Tumor Necrosis Factor-alpha
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Thromboplastin
  • nintedanib
Topics
  • Carotid Arteries (drug effects, metabolism)
  • Carrier Proteins (genetics, metabolism)
  • Cell Movement (drug effects, genetics)
  • Cell Proliferation (drug effects)
  • Cells, Cultured
  • Endothelial Cells (drug effects, metabolism)
  • Endothelium, Vascular (drug effects, metabolism)
  • Gene Expression Regulation (drug effects, genetics)
  • Humans
  • Indoles (pharmacology)
  • Inflammation (genetics, metabolism)
  • Intracellular Signaling Peptides and Proteins
  • NF-kappa B (genetics, metabolism)
  • Neoplasm Proteins (genetics, metabolism)
  • Neovascularization, Pathologic (genetics, metabolism)
  • Phosphorylation (drug effects, genetics)
  • Serum Amyloid A Protein (genetics, metabolism)
  • Thromboplastin (genetics, metabolism)
  • Tumor Necrosis Factor-alpha (genetics, metabolism)
  • Vascular Endothelial Growth Factor A (genetics, metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: